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Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell

Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein c...

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Autores principales: Pezeshkian, Weria, Shillcock, Julian C., Ipsen, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309782/
https://www.ncbi.nlm.nih.gov/pubmed/34203472
http://dx.doi.org/10.3390/toxins13070449
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author Pezeshkian, Weria
Shillcock, Julian C.
Ipsen, John H.
author_facet Pezeshkian, Weria
Shillcock, Julian C.
Ipsen, John H.
author_sort Pezeshkian, Weria
collection PubMed
description Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein complexes is essential not only for understanding their biological functions but also for the rational design of targeted drug delivery vehicles that must navigate across the cell membrane to deliver their therapeutic payload. Despite the immense advances in experimental techniques, the investigations of the toxin entry mechanism have remained challenging. Computer simulations are robust complementary tools that allow for the exploration of biological processes in exceptional detail. In this review, we first highlight the strength of computational methods, with a special focus on all-atom molecular dynamics, coarse-grained, and mesoscopic models, for exploring different stages of the toxin protein entry mechanism. We then summarize recent developments that are significantly advancing our understanding, notably of the glycolipid–lectin (GL-Lect) endocytosis of bacterial Shiga and cholera toxins. The methods discussed here are also applicable to the design of membrane-penetrating nanoparticles and the study of the phenomenon of protein phase separation at the surface of the membrane. Finally, we discuss other likely routes for future development.
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spelling pubmed-83097822021-07-25 Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell Pezeshkian, Weria Shillcock, Julian C. Ipsen, John H. Toxins (Basel) Review Many bacteria secrete toxic protein complexes that modify and disrupt essential processes in the infected cell that can lead to cell death. To conduct their action, these toxins often need to cross the cell membrane and reach a specific substrate inside the cell. The investigation of these protein complexes is essential not only for understanding their biological functions but also for the rational design of targeted drug delivery vehicles that must navigate across the cell membrane to deliver their therapeutic payload. Despite the immense advances in experimental techniques, the investigations of the toxin entry mechanism have remained challenging. Computer simulations are robust complementary tools that allow for the exploration of biological processes in exceptional detail. In this review, we first highlight the strength of computational methods, with a special focus on all-atom molecular dynamics, coarse-grained, and mesoscopic models, for exploring different stages of the toxin protein entry mechanism. We then summarize recent developments that are significantly advancing our understanding, notably of the glycolipid–lectin (GL-Lect) endocytosis of bacterial Shiga and cholera toxins. The methods discussed here are also applicable to the design of membrane-penetrating nanoparticles and the study of the phenomenon of protein phase separation at the surface of the membrane. Finally, we discuss other likely routes for future development. MDPI 2021-06-28 /pmc/articles/PMC8309782/ /pubmed/34203472 http://dx.doi.org/10.3390/toxins13070449 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pezeshkian, Weria
Shillcock, Julian C.
Ipsen, John H.
Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title_full Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title_fullStr Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title_full_unstemmed Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title_short Computational Approaches to Explore Bacterial Toxin Entry into the Host Cell
title_sort computational approaches to explore bacterial toxin entry into the host cell
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309782/
https://www.ncbi.nlm.nih.gov/pubmed/34203472
http://dx.doi.org/10.3390/toxins13070449
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